Interaction of Transforming Growth Factor β Receptors with Apolipoprotein J/Clusterin

Proteins mediating the transmission of the signal from an activated transforming growth factor β (TGFβ) receptor complex have not been identified. Using a yeast interaction screen to search for proteins that associate with the type II TGFβ receptor (RII), we isolated a protein which was identical to apolipoprotein J (apoJ)/clusterin. ApoJ interacts with both the type I (RI) and type II (RII) TGFβ receptors but does not interact with the epidermal growth factor (EGF) receptor. The interaction between RII and apoJ occurs through the C-terminal 127 amino acids of RII. Deletion of this region, which contains the kinase insert 2 domain, abrogates binding to apoJ. The binding of apoJ to either the RI and the RII receptors is direct, not requiring other proteins, and is not specific for the α or β subunit of apoJ since both subunits are effective in competing for binding. RI and RII fusion proteins are capable of precipitating the 60 kDa intracellular form of apoJ from [35S]methionine-labeled cellular lysates, suggesting that this form of the protein may play some role in TGFβ signaling or TGFβ receptor processing.